Interactions between signal transduction pathways involving calcium mobilization, and pathways that involve activation of protein tyrosine kinases were studied. In NIH 3T3 cells, the marine toxin maitotoxin (MTX), and PGF2alpha activate phosphoinositide breakdown and induce tyrosine phosphorylation of several protein substrates as determined by immunoprecipitation of [32P]orthophosphate-labeled cells with an antiphosphotyrosine antibody. Among the substrates subject to tyrosine phosphorylation after PGF2alpha, phospholipase C-gamma (PLCbeta) was identified by combination of immunoprecipitation with an antiphosphotyrosine antibody and subsequent immunoblot with an antiphospholipase C-gamma antibody. The stimulation of protein tyrosine phosphorylation is dependent on the presence of extracellular calcium and it can be inhibited by the blocker of receptor-operated calcium channels SK&F 96365. PGF2alpha-induced phosphoinositide breakdown is primarily attained through a receptor coupled to a G protein which in turn activates most likely PLC~. However, PGF2alpha-mediated phosphoinositide breakdown is partially inhibited by SK&F96365 and is reduced in the absence of calcium. These results suggest that PLCbeta may play a role in PGF2alpha- induced stimulation and are reminiscent of effects observed with growth factors. Stimulation of tyrosine kinase activity may be involved in cell proliferation observed with PGF2alpha. In contrast to PGF2alpha, PGE1 is inactive in stimulating phosphoinositide breakdown in NIH 3T3 cells. However, PGE1 induces elevation of intracellular calcium. Such response is dependent on the presence of extracellular calcium and it can be blocked by L-type channel blockers like nifedipine and methoxyverapamil. PGE1 also stimulates the accumulation of cyclic AMP in these cells. The activation of calcium influx, however was not mimicked by agents that elevate cyclic AMP, like forskolin and IBMX. Therefore, in NIH 3T3 cells a receptor for PGE1 is linked to the opening of an L-type-like calcium channel. This channel is not sensitive to depolarization with high concentrations of K+, but it can be activated by the dihydropyridine BAY K 8644. This PGE1-mediated regulation of a calcium channel represents a novel mechanism for PG receptor signalling.